Lorlatinib Shows Promise Against Brain Metastases in ALK+ Lung Cancer

Lorlatinib exhibits durable responses in pretreated patients with ALK-positive non–small-cell lung cancer (NSCLC) and promising intracranial activity and tumor responses in those patients who have brain metastases, regardless of prior therapy, according to findings from a phase I/II clinical study (abstract 9006) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.

“Lorlatinib demonstrated clinically meaningful and durable responses in ALK-positive patients receiving one or more prior ALK TKI [tyrosine kinase inhibitor], many of whom were heavily pretreated,” said coauthor Sai-Hong Ignatius Ou, MD, of the University of California Irvine Chao Family Comprehensive Cancer Center in Orange, California.

Lorlatinib is a selective and potent next-generation ALK/ROS1 TKI. The US Food and Drug Administration has granted it a Breakthrough Therapy Designation for patients with ALK-positive metastatic NSCLC who were previously treated with at least one line of ALK TKI therapy.

The authors enrolled 199 patients and assigned them to 6 expansion cohorts for study. Efficacy data were available for 82 patients at analysis. Sixty-two patients had brain metastases.

Treatment was safe and tolerable. “The most common adverse event was hyperlipidemia, successfully managed with lipid-lowering agents,” Ou explained. “Cognitive effects were generally mild and rapidly reversible upon dose modifications. Permanent discontinuations of treatment due to adverse events were infrequent.”

Treatment-related adverse events affected 113 patients, resulting in dose delays for 29% of patients, dose reductions in 20% of patients, and discontinuation in 3.4% of patients. The most common treatment-related adverse events were hypercholesterolemia, hypertriglyceridemia, peripheral edema, peripheral neuropathy, cognitive and mood effects, and weight gain.

The confirmed overall response rate (ORR) for ALK-positive patients who had received previous ALK TKI treatment was 32.9% but best overall response had not yet been determined for 13% of patients at the time of analysis, Ou cautioned. Duration of response data were not mature.